Protective immunity to Bordetella pertussis requires both B cells and CD4+ T cells for key functions other than specific antibody production

Protective immunity to Bordetella pertussis requires both B cells and CD4+ T cells for key functions other than specific antibody production
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DOI:
10.1084/jem.191.11.1841
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发表时间:
2000-06-05
影响因子:
15.3
通讯作者:
Shahin, RD
Shahin, RD
中科院分区:
医学1区
文献类型:
--
作者:
Leef, M;Elkins, KL;Shahin, RD

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为了探讨百日咳杆菌保护性免疫的基本性质,我们研究了用福尔马林固定的B鼻内免疫成年小鼠。百日咳(FFBP),然后是气雾剂B。百日咳攻毒。小鼠鼻内给予两个剂量的FFBP完全清除随后的百日咳气溶胶挑战气管和肺(定义为保护),但特异性抗体水平和细菌清除率之间没有相关性。此外,在气溶胶激发前转移免疫血清对细菌负荷的影响最小。然而,在FFBP免疫小鼠的引流淋巴结中检测到产生干扰素γ但不产生白细胞介素4或白细胞介素10的百日咳特异性T细胞。值得注意的是,B细胞敲除(BKO)小鼠的重复免疫导致部分保护,并且通过转移百日咳免疫B细胞重建完全保护;重建的BKO小鼠几乎没有任何可检测的抗百日咳抗体。免疫缺乏所有T细胞或缺乏CD 4(+)T细胞的小鼠确实导致保护;相反,CD 8(-)小鼠受到保护。在免疫后但在气溶胶攻击前耗尽CD 4(+)T细胞的小鼠,因此具有正常量的特异性抗体,没有得到最佳保护。综上所述,这些数据表明,百日咳的保护性免疫依赖于CD 4(+)T细胞和B细胞,这两种细胞类型除了产生特异性抗体外还提供重要的功能。
To investigate the fundamental nature of protective immunity to Bordetella pertussis, we studied intranasal immunization of adult mice with formalin-fixed B. pertussis (FFBP), followed by aerosol B. pertussis challenge. Mice given two doses of FFBP intranasally completely cleared a subsequent pertussis aerosol challenge from tracheae and lungs (defined as protection), but there was no correlation between levels of specific antibody and clearance of bacteria. Further, transfer of immune serum before aerosol challenge had minimal effects on bacterial burdens. However, pertussis-specific T cells producing interferon gamma but not interleukin 4 or interleukin 10 were detected in draining lymph nodes of FFBP-immunized mice. Significantly, repeated immunization of B cell knockout (BKO) mice resulted in partial protection, and complete protect ion was reconstituted by transfer of pertussis-immune B cells; reconstituted BKO mice had little ii any detectable antipertussis antibodies. Immunization of mice lacking all T cells or lacking CD4(+) T cells did trot lead to protection; in contrast, CD8(-) mice were protected. Mice depleted of CD4(+) T cells after immunization but before aerosol challenge, which thus had normal amounts of specific antibodies, were not optimally protected. Taken together, these data indicate that protective immunity to pertussis is dependent on both CD4(+) T cells and B cells, and both cell types provide significant functions other than specific antibody production.